The component studies in this Program Project on the genetics of early cardiac development share a technical and biological focus on the mouse as the organism studied. Among vertebrates, only the mouse permits so robust a range of genetic manipulations. The projects involve creating mutations in the germ line and somatic tissues of mice by performing homologous recombination in ES cells, or Cre/IoxP recombination in vivo. Other needs include the creation of mice harboring a bacterial artificial chromosome (BAC), conventional transgene, inducible transgene, or engineered cells that are introduced into blastocysts. These procedures for manipulation of ES cells and the construction of mice are technically demanding and most efficiently performed in a dedicated core laboratory. All of these alleles and technologies have been successfully implemented by the Core Directors, and many of the specific innovations were developed through prior support of this Project.